Bioactive Materials (Apr 2022)

A multiplexed circulating tumor DNA detection platform engineered from 3D-coded interlocked DNA rings

  • Sha Yang,
  • Xinyu Zhan,
  • Xiaoqi Tang,
  • Shuang Zhao,
  • Lianyu Yu,
  • Mingxuan Gao,
  • Dan Luo,
  • Yunxia Wang,
  • Kai Chang,
  • Ming Chen

Journal volume & issue
Vol. 10
pp. 68 – 78

Abstract

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Circulating tumor DNA (ctDNA) is a critical biomarker not only important for the early detection of tumors but also invaluable for personalized treatments. Currently ctDNA detection relies on sequencing. Here, a platform termed three-dimensional-coded interlocked DNA rings (3D-coded ID rings) was created for multiplexed ctDNA identification. The ID rings provide a ctDNA recognition ring that is physically interlocked with a reporter ring. The specific binding of ctDNA to the recognition ring initiates target-responsive cutting via a restriction endonuclease; the cutting then triggers rolling circle amplification on the reporter ring. The signals are further integrated with internal 3D codes for multiplexed readouts. ctDNAs from non-invasive clinical specimens including plasma, feces, and urine were detected and validated at a sensitivity much higher than those obtained through sequencing. This 3D-coded ID ring platform can detect any multiple DNA fragments simultaneously without sequencing. We envision that our platform will facilitate the implementation of future personalized/precision medicine.

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